Organics

19 pages, 3182 KB

Open AccessArticle

Synthesis and In Silico Evaluation of the Ninhydrin Derivatives Interaction with Target Proteins Involved in Cancer Pathogenesis and Progression

by Anastasia R. Kovrizhina and Andrei I. Khlebnikov

Organics 2026, 7(2), 26; https://doi.org/10.3390/org7020026 - 18 Jun 2026

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Abstract

Ninhydrins represent a promising chemical space for the search for new biologically active molecules with antimicrobial, antiprotease, and antitumor properties. In the present work, new ninhydrin derivatives were synthesized, and for the first time, a systematic in silico study of ninhydrins as multitarget [...] Read more.

Ninhydrins represent a promising chemical space for the search for new biologically active molecules with antimicrobial, antiprotease, and antitumor properties. In the present work, new ninhydrin derivatives were synthesized, and for the first time, a systematic in silico study of ninhydrins as multitarget ligands for five pharmacologically significant targets (HER1/HER4, HER2/HER3, Trk-B, PPAR-α, and LTβR) was conducted, whose amplification or overexpression plays a key role in the pathogenesis and progression of certain aggressive cancer types. Among the studied ninhydrin derivatives, compound 1 (2,2-dihydroxy-5,6-dimethoxy-1H-indene-1,3(2H)-dione) stands out as the most potentially active molecule. It exhibits high affinity for HER1/HER4, Trk-B, and PPAR-α, opening up potential applications in oncology (HER family and Trk-B inhibition during BDNF overexpression), neurodegenerative diseases (Trk-B modulation), and metabolic disorders (PPAR-α activation). Compound 4 (2,2-Dihydroxy-5-trifluoromethylindane-1,3-dione) is a leader in LTβR binding and also holds promise for immuno-oncology and anti-inflammatory strategies. Full article

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15 pages, 2884 KB

Open AccessArticle

Controlling Site Selectivity in the Phosphorylation of Amphiphilic Diols: Aminopyridine Organocatalysts vs. Stoichiometric Amine Bases

by Shai Ben Sasson, Noa Naama, Mikhail Kozlov, Ibrahim Amer and Moshe Portnoy

Organics 2026, 7(2), 25; https://doi.org/10.3390/org7020025 - 11 Jun 2026

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Abstract

Our recent studies demonstrated that dialkylaminopyridine organocatalysts featuring an extensive secondary sphere preferentially phosphorylate the alcohol at the apolar domain of a model amphiphilic diol. In the present study, this site-selective behavior was corroborated across a broader range of amphiphilic diols. Furthermore, we [...] Read more.

Our recent studies demonstrated that dialkylaminopyridine organocatalysts featuring an extensive secondary sphere preferentially phosphorylate the alcohol at the apolar domain of a model amphiphilic diol. In the present study, this site-selective behavior was corroborated across a broader range of amphiphilic diols. Furthermore, we found that the site selectivity can be inverted by applying certain saturated aliphatic amine bases in stoichiometric amounts. Screening identified cis-2,6-dimethylpiperidine as the most selective promoter, consistently inducing phosphorylation at the polar domain across all tested diols. Remarkably, despite being a secondary amine, this base did not produce any detectable phosphoramidate byproduct. Full article

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13 pages, 8439 KB

Open AccessArticle

Synthesis, Molecular Structure and Crystal Packing Peculiarities of Some 5-Arylidene-3-phenylrhodanine Derivatives

by Xiumei Bai, Danila R. Chernyavskiy, Anna D. Maksimova, Ilya A. Yakushev, Viktor A. Tafeenko, Elena K. Beloglazkina and Alexander V. Finko

Organics 2026, 7(2), 24; https://doi.org/10.3390/org7020024 - 8 Jun 2026

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Abstract

We report the synthesis and single-crystal X-ray structures of three novel (Z)-5-arylidene-3-phenylrhodanine derivatives, differing in the substituents on the benzylidene fragment (two methoxy groups (compound I), a dioxine ring (compound II), or a dioxole ring (compound III)). Despite [...] Read more.

We report the synthesis and single-crystal X-ray structures of three novel (Z)-5-arylidene-3-phenylrhodanine derivatives, differing in the substituents on the benzylidene fragment (two methoxy groups (compound I), a dioxine ring (compound II), or a dioxole ring (compound III)). Despite the overall similarity of the molecules, their supramolecular architectures were found out to be strikingly different. The results of intermolecular interactions in those structures are investigated via Hirshfeld surface, molecular electrostatic potential surface and non-covalent interaction analyses. The fine modulation of the arylidene substituent can switch the primary intermolecular synthon from weak S···S bonding to n···π* interactions, offering new possibilities for crystal engineering of rhodanine-based materials. Full article

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16 pages, 17449 KB

Open AccessArticle

Marine-Biomass-Derived Melanin–Chitosan Composites as Natural Black Hair Colorants: Charge Reversal and Electrostatic Deposition Mechanism

by Toshihiko Matsuura and Airi Nakajima

Organics 2026, 7(2), 23; https://doi.org/10.3390/org7020023 - 8 Jun 2026

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Abstract

Conventional oxidative hair dyes rely on aromatic amines, raising concerns about human health and environmental safety. This study reports a natural hair-coloring system using size-controlled ink particles (SIPs, ~170 nm in diameter) from cuttlefish ink and chitosan. Because both SIPs and hair surfaces [...] Read more.

Conventional oxidative hair dyes rely on aromatic amines, raising concerns about human health and environmental safety. This study reports a natural hair-coloring system using size-controlled ink particles (SIPs, ~170 nm in diameter) from cuttlefish ink and chitosan. Because both SIPs and hair surfaces carry negative charges near neutral pH, original SIPs exhibited poor deposition onto hair. Polyelectrolyte complexation with chitosan reversed the SIP surface charge under acidic conditions (maximum ζ ≈ +41 mV at pH 2.4), enabling electrostatic deposition onto hair fibers. Dynamic light scattering (DLS) revealed pH-responsive aggregation at pH 1.6–1.8 and redispersion at pH 2.8–4.3, while ultraviolet–visible (UV–Vis) spectra confirmed that the broadband absorption of melanin was preserved, consistent with predominantly noncovalent interactions. Scanning electron microscopy (SEM) showed a particle-based composite coating on hair fibers. An optimal SIP:chitosan weight ratio of 10:1 at pH ~4.7 yielded the darkest and most uniform coloration (L* = 32.89, ΔE*_ab = 55.89) without metallic mordants, achieving darker coloration than representative plant-based natural colorants reported in the literature. These results demonstrate a marine-biomass-derived approach to natural black hair coloration with strong darkening performance. Full article

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9 pages, 1495 KB

Open AccessCommunication

Palladium-Catalyzed Enantiospecific Three-Component Reaction for the Synthesis of 1,2,4-Trisubstituted Homoallylic Alcohols

by Ayumu Natsubori, Momoka Ikeda, Yushin Hosokawa, Mizuki Akagawa and Yoshikazu Horino

Organics 2026, 7(2), 22; https://doi.org/10.3390/org7020022 - 27 May 2026

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Abstract

1,2,4-Trisubstituted chiral homoallylic alcohols are valuable intermediates in natural product synthesis and complex molecular architectures; however, their catalytic asymmetric synthesis remains challenging due to the need for precise control of regioselectivity, diastereoselectivity, E/Z geometry, and enantioselectivity. Herein, we report a palladium-catalyzed [...] Read more.

1,2,4-Trisubstituted chiral homoallylic alcohols are valuable intermediates in natural product synthesis and complex molecular architectures; however, their catalytic asymmetric synthesis remains challenging due to the need for precise control of regioselectivity, diastereoselectivity, E/Z geometry, and enantioselectivity. Herein, we report a palladium-catalyzed enantiospecific three-component reaction of aldehydes, borylated allyl acetates, and dimethylzinc for the efficient synthesis of 1,2,4-trisubstituted anti-(Z)-homoallylic alcohols. The present method employs readily accessible chiral borylated allyl acetates and proceeds with high levels of stereochemical control, providing a practical approach to structurally complex homoallylic alcohols. Full article

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19 pages, 3345 KB

Open AccessArticle

Adsorption and Electronic Structure of Imidazole-Based Inhibitors on Fe(100): A Combined DFT and DFTB Study

by Andrea Navarrete-Mosquera, Juan Pedro Palomares-Báez, Rody Soto-Rojo, Tomás Delgado-Montiel, Samuel Soto-Acosta, Nora Aydee Sánchez-Bojorge, Daniel Glossman-Mitnik and Jesús Baldenebro-López

Organics 2026, 7(2), 21; https://doi.org/10.3390/org7020021 - 25 May 2026

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Abstract

This study presents a theoretical investigation of the adsorption and electronic structure of two imidazole derivatives, 4-(1,4,5-triphenylimidazol-2-yl)-aniline (M1) and N,N-dimethyl-4-(1,4,5-triphenylimidazol-2-yl)-aniline (M2), on an Fe(100) surface. A combined computational approach, employing Density Functional Theory for molecular reactivity, Density-Functional Tight-Binding for surface [...] Read more.

This study presents a theoretical investigation of the adsorption and electronic structure of two imidazole derivatives, 4-(1,4,5-triphenylimidazol-2-yl)-aniline (M1) and N,N-dimethyl-4-(1,4,5-triphenylimidazol-2-yl)-aniline (M2), on an Fe(100) surface. A combined computational approach, employing Density Functional Theory for molecular reactivity, Density-Functional Tight-Binding for surface interactions, and Molecular Dynamics (MD) simulations for binding stability, was utilized to provide a comprehensive analysis. Quantum–chemical calculations indicate that both inhibitors exhibit strong donor characteristics, with M2 consistently demonstrating greater potential. This enhanced performance is attributed to the strong electron-donating nature and increased structural planarity conferred by the dimethylamine group in M2, which results in a lower HOMO-LUMO energy gap and higher chemical reactivity. Analysis of the inhibitor-surface interaction confirmed a strong electron donor-acceptor mechanism, indicative of stable chemical bond formation and a predominant chemisorption process. MD simulations revealed that both molecules form stable adsorption layers on the iron surface, suggesting initial adsorption behavior. Full article

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13 pages, 361 KB

Open AccessCommunication

Design, Synthesis, and Drug-Likeness Assessment of Azole-Functionalized Hydrazone Derivatives: Towards Antimicrobial Activity

by Juozas Kiltinavičius, Kristina Kantminienė, Ilona Jonuškienė and Ingrida Tumosienė

Organics 2026, 7(2), 20; https://doi.org/10.3390/org7020020 - 18 May 2026

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Abstract

Reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with selected aldehydes and ketone provided novel hydrazone derivatives bearing azole moieties: pyrazole, pyrrole, and indole. The drug likeness of the newly synthesized compounds and their physicochemical characteristics were examined to fit Lipinski’s Rule of Five. N-(2,5-dimethyl-1H-pyrrol-1-yl)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carboxamide [...] Read more.

Reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with selected aldehydes and ketone provided novel hydrazone derivatives bearing azole moieties: pyrazole, pyrrole, and indole. The drug likeness of the newly synthesized compounds and their physicochemical characteristics were examined to fit Lipinski’s Rule of Five. N-(2,5-dimethyl-1H-pyrrol-1-yl)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carboxamide (5) exhibited the most favorable overall ADMET profile, combining compliance with key physicochemical requirements for antimicrobial activity with superior solubility and reduced predicted hepatotoxicity and nephrotoxicity. Despite generally elevated plasma protein binding across the series, this compound provided the most advantageous balance between permeability, systemic exposure, and safety. Full article

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16 pages, 3749 KB

Open AccessArticle

Integrated In Silico and Chromatographic Evaluation of the Biological Properties of Novel Bis-Substituted Thiocarbohydrazone Derivatives

by Suzana Apostolov, Dragana Mekić, Gorana Mrđan and Gyöngyi Vastag

Organics 2026, 7(2), 19; https://doi.org/10.3390/org7020019 - 12 May 2026

Viewed by 701

Abstract

Thiocarbohydrazone derivatives represent a highly significant class in medicinal chemistry, characterized by a versatile scaffold defined with a thiocarbonyl (C=S) core and one or two imine (–C=N–) functionalities, allowing for precise modulation of their physicochemical and biological properties. The biological potential of a [...] Read more.

Thiocarbohydrazone derivatives represent a highly significant class in medicinal chemistry, characterized by a versatile scaffold defined with a thiocarbonyl (C=S) core and one or two imine (–C=N–) functionalities, allowing for precise modulation of their physicochemical and biological properties. The biological potential of a series of novel bis-substituted thiocarbohydrazone derivatives was predicted and evaluated through comprehensive in silico analysis. All investigated compounds complied with Lipinski’s Rule of 5, with most also satisfying the Rule of 3 while simultaneously exhibiting favorable pharmacokinetic properties and low predicted ecotoxicity. To substantiate these findings and elucidate the influence of para-substituents, chromatographic behavior of the studied derivatives was evaluated using reversed-phase thin-layer chromatography (RP-TLC). Initial linear regression analysis revealed statistically significant correlations between chromatographic parameters and in silico-derived descriptors of lipophilicity, pharmacokinetics, and ecotoxicity. Furthermore, cluster analysis and principal component analysis provided a robust and unambiguous interpretation of the structure–property relationships, highlighting substituent polarity as the leading factor controlling the bioactivity of bis-substituted thiocarbohydrazones, although the contribution of electronic effects cannot be neglected. Moreover, R_M⁰ correlates with lipophilicity and pharmacokinetics, whereas m reflects ecotoxicity. Collectively, these findings emphasize the critical role of subtle structural variations in shaping the overall properties of these novel derivatives. Full article

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12 pages, 822 KB

Open AccessArticle

Synthesis of 23,23-Difluoro-24-nor- and 24′,24′-Difluoro-24-Homovitamin D₃ Analogues and Unexpected Structure-Activity Relationships

by Fumihiro Kawagoe, Hiroya Tabuchi, Taiyo Ideguchi, Yuki Okamoto, Souma Murata, Tomofumi Yatsu, Syota Yamada, Kaori Yasuda, Yusuke Akagi, Masashi Takano, Toshie Fujishima, Yoshiki Miyata, Ken’ichi Aoki, Toshiyuki Sakaki and Atsushi Kittaka

Organics 2026, 7(2), 18; https://doi.org/10.3390/org7020018 - 27 Apr 2026

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Abstract

We synthesized two vitamin D₃ analogues, 3 and 4, which have a shortened or elongated fluoro-side-chain based on 24,24-difluoro-25-hydroxyvitamin D₃ (5) using an efficient convergent approach and studied their preliminary biological activity. Both analogues exhibited greater resistance to [...] Read more.

We synthesized two vitamin D₃ analogues, 3 and 4, which have a shortened or elongated fluoro-side-chain based on 24,24-difluoro-25-hydroxyvitamin D₃ (5) using an efficient convergent approach and studied their preliminary biological activity. Both analogues exhibited greater resistance to CYP24A1-mediated metabolism than the natural 25-hydroxyvitamin D₃ (6), although their stability was lower than that of 5. Analogue 3 showed an approximately 100-fold lower human vitamin D receptor (hVDR)-binding affinity compared with 5 and 6. Despite this marked reduction in VDR-binding affinity, it demonstrated an approximately 1.5-fold increase in VDR-ligand binding domain (LBD) transcriptional activation of the natural ligand 6. In contrast, analogue 4 displayed moderate VDR-binding affinity and VDR-LBD transactivation compared with 5 and 6. We found that compound 3 is a unique vitamin D analogue with a fluorinated and shortened side-chain, exhibiting low binding affinity for hVDR but potent transcriptional activity through VDR-LBD with its long half-life; thus, 3 may serve as a basic structural skeleton for advancing medicinal chemistry and drug discovery. Full article

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8 pages, 686 KB

Open AccessArticle

Revised Formal Total Synthesis of Dehydro-δ-Viniferin and Anigopreissin A

by Alessandro Santarsiere, Marianna Volgare and Lucia Chiummiento

Organics 2026, 7(2), 17; https://doi.org/10.3390/org7020017 - 16 Apr 2026

Cited by 1 | Viewed by 841

Abstract

This work presents a revised total synthesis of two pharmacologically relevant benzofurans using newly developed environmentally friendly methodologies. In particular, we focused on establishing improved synthetic routes to stilbene dimers under milder and more sustainable reaction conditions. During our investigations, we optimized an [...] Read more.

This work presents a revised total synthesis of two pharmacologically relevant benzofurans using newly developed environmentally friendly methodologies. In particular, we focused on establishing improved synthetic routes to stilbene dimers under milder and more sustainable reaction conditions. During our investigations, we optimized an efficient Sonogashira coupling carried out in water, which, followed by a Suzuki-like reaction conducted in dimethyl carbonate (DMC) in the absence of any transition metals, served as the key step for the synthesis of the benzofuran core. Full article

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56 pages, 7096 KB

Open AccessReview

Recent Developments in Chemical Synthesis and Biological Activities of Aloe-Emodin Derivatives

by Jeltzlin Semerel, Nigel John, Pedro Fardim and Wim Dehaen

Organics 2026, 7(2), 16; https://doi.org/10.3390/org7020016 - 10 Apr 2026

Cited by 2 | Viewed by 1392

Abstract

Aloe-emodin is an anthraquinone with a wide range of medicinal applications, including anti-angiogenic, anticancer, antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. In this review, the functionalization of aloe-emodin using various synthetic methods, including alkylation, condensation, esterification, the Finkelstein reaction, and the Kabachnik–Fields reaction was [...] Read more.

Aloe-emodin is an anthraquinone with a wide range of medicinal applications, including anti-angiogenic, anticancer, antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. In this review, the functionalization of aloe-emodin using various synthetic methods, including alkylation, condensation, esterification, the Finkelstein reaction, and the Kabachnik–Fields reaction was reported. The biological activity of the synthesized aloe-emodin derivatives is discussed, with a focus on their potential future applications as anticancer agents, enzyme inhibitors, anti-inflammatory agents, and antimicrobial agents. This review also discusses the structure–activity relationship (SAR) and the mechanism of action (e.g., molecular docking studies, cell membrane-disrupting capacity, and apoptosis studies). This review highlights the many contributions made towards the design and development of novel, biologically active aloe-emodin derivatives. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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35 pages, 10285 KB

Open AccessArticle

Synthesis, Characterization, and Multidimensional In Silico Evaluation of Novel Etodolac-Based 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents

by Tiba M. Hameed, Rafid M. Hashim, S. J. Abed, Raneen Hashim Ridha and O. Al-Mohammed Baqer

Organics 2026, 7(2), 15; https://doi.org/10.3390/org7020015 - 7 Apr 2026

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Abstract

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD [...] Read more.

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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Organics, Volume 7, Issue 2 (June 2026) – 12 articles

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